Summary: Objectives: Although pertussis vaccines containing a whole-cell pertussis component effectively controlled pertussis disease in the US, safety concerns led to an international research and development effort that resulted in the US licensure in 1996-2002 of five DTP products with an acellular pertussis component. Progress in the development and licensing of less reactogenic acellular pertussis vaccines, as well as combination vaccines containing an acellular pertussis component, was hindered by the lack of a laboratory correlate of clinical protection and of standardized assays for measurement of immune responses. To address this need, the Laboratory has continued a long-term research project with the following aims: a) To work toward the international standardization of immunoassays used to evaluate the antigen and isotype specific responses to Bordetella pertussis. b) To employ these assays to evaluate the serologic response in individuals immunized with pertussis vaccine. c) To develop new assays to measure human immune response to vaccine. d) To investigate new animal models that may provide a laboratory correlate of clinical protection. e) To establish suitable vaccine potency assays. FY02 activities: 1) Continued evaluation of a mouse leukocytosis model that is able to detect pertussis toxin (PT)-neutralizing antibodies in serum, correlating these results with the anti-PT binding activity of the same sera, as measured by ELISA. This model is being applied to the study of the cross-boosting by inactivated pertussis toxin contained in licensed DTaP vaccines. 2) Completed evaluation of the data from a previously published international collaborative study that evaluated immunoassays used in acellular pertussis vaccine efficacy and immunogenicity studies. The data were used to evaluate a statistical model that related the coefficient of variation and the probability of observing a k-fold difference among repeated measurements. A manuscript describing the statistical approach has been accepted for publication. 3) Provided ongoing technical advice and support for CDC contract entitled: "Measurement of antibodies to three antigens of Bordetella pertussis." The goal of the study is to develop pertussis serodiagnostic assays that can be transferred to state and regional clinical laboratories.